scholarly journals Naturalistic coding of working memory in primate prefrontal cortex

2020 ◽  
Author(s):  
Megan Roussy ◽  
Rogelio Luna ◽  
Lyndon Duong ◽  
Benjamin Corrigan ◽  
Roberto A. Gulli ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Memory Performance ◽  
Memory Function ◽  
Nmda Receptor Antagonist ◽  
Inhibitory Neurons ◽  
Natural Behavior ◽  
Neuronal Populations ◽  
Memory Representations ◽  
Decoding Accuracy

SummaryThe primate lateral prefrontal cortex (LPFC) is considered fundamental for temporarily maintaining and manipulating mental representations that serve behavior, a cognitive function known as working memory1. Studies in non-human primates have shown that LPFC lesions impair working memory2 and that LPFC neuronal activity encodes working memory representations3. However, such studies have used simple displays and constrained gaze while subjects held information in working memory3, which put into question their ethological validity4,5. Currently, it remains unclear whether LPFC microcircuits can support working memory function during natural behavior. We tested macaque monkeys in a working memory navigation task in a life-like virtual environment while their gaze was unconstrained. We show that LPFC neuronal populations robustly encode working memory representations in these conditions. Furthermore, low doses of the NMDA receptor antagonist, ketamine, impaired working memory performance while sparing perceptual and motor skills. Ketamine decreased the firing of narrow spiking inhibitory interneurons and increased the firing of broad spiking cells reducing population decoding accuracy for remembered locations. Our results show that primate LPFC generates robust neural codes for working memory in naturalistic settings and that such codes rely upon a fine balance between the activation of excitatory and inhibitory neurons.

scholarly journals Time-invariant working memory representations in the presence of code-morphing in the lateral prefrontal cortex

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aishwarya Parthasarathy ◽  
Cheng Tang ◽  
Roger Herikstad ◽  
Loong Fah Cheong ◽  
Shih-Cheng Yen ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Dimensional Subspace ◽  
Neural Data ◽  
Neuronal Populations ◽  
Attractor Model ◽  
Memory Representations ◽  
Low Dimensional ◽  
Types Of Information ◽  
Time Invariant

Abstract Maintenance of working memory is thought to involve the activity of prefrontal neuronal populations with strong recurrent connections. However, it was recently shown that distractors evoke a morphing of the prefrontal population code, even when memories are maintained throughout the delay. How can a morphing code maintain time-invariant memory information? We hypothesized that dynamic prefrontal activity contains time-invariant memory information within a subspace of neural activity. Using an optimization algorithm, we found a low-dimensional subspace that contains time-invariant memory information. This information was reduced in trials where the animals made errors in the task, and was also found in periods of the trial not used to find the subspace. A bump attractor model replicated these properties, and provided predictions that were confirmed in the neural data. Our results suggest that the high-dimensional responses of prefrontal cortex contain subspaces where different types of information can be simultaneously encoded with minimal interference.

scholarly journals Chemogenetic actuator drugs impair prefrontal cortex-dependent working memory in rhesus monkeys

2019 ◽  
Author(s):  
Nicholas A. Upright ◽  
Mark G. Baxter
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Rhesus Monkeys ◽  
Memory Performance ◽  
Memory Function ◽  
Muscarinic Acetylcholine Receptor ◽  
Designer Drugs ◽  
Delayed Response ◽  
Response Task ◽  
Delayed Response Task

AbstractThe most common chemogenetic neuromodulatory system, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is no longer sensitive to acetylcholine. It is crucial in studies using these systems to test the potential effects of DREADD actuators prior to any DREADD transduction, so that effects of DREADDs can be attributed to the chemogenetic system rather than the actuator drug. We investigated working memory performance after injections of three DREADD agonists, clozapine, olanzapine, and deschloroclozapine, in male rhesus monkeys tested in a spatial delayed response task. Performance at 0.1 mg/kg clozapine and 0.1 mg/kg deschloroclozapine did not differ from mean performance after vehicle in any of the four subjects. Administration of 0.2 mg/kg clozapine impaired working memory function in three of the four monkeys. Two monkeys were impaired after administration of 0.1 mg/kg olanzapine and two monkeys were impaired after the 0.3 mg/kg dose of deschloroclozapine. We speculate that the unique neuropharmacology of prefrontal cortex function makes the primate prefrontal cortex especially vulnerable to off-target effects of DREADD actuator drugs with affinity for endogenous monoaminergic receptor systems. These findings underscore the importance of within-subject controls for DREADD actuator drugs to confirm that effects following DREADD receptor transduction are not due to the actuator drug itself, as well as validating the behavioral pharmacology of DREADD actuator drugs in the specific tasks under study.Significance StatementChemogenetic technologies, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), allow for precise and remote manipulation of neuronal circuits. In the present study, we tested monkeys in a spatial delayed response task after injections of three actuator drugs – clozapine, olanzapine, and deschloroclozapine. We found that monkeys showed significant working memory impairments after 0.2 mg/kg clozapine, 0.1 mg/kg olanzapine, and 0.3 mg/kg deschloroclozapine compared to vehicle performance. In monkeys that showed impairments, these deficits were particularly apparent at longer delay periods. It is imperative to validate the drugs and dosages in the particular behavioral test to ensure any behavior after DREADD transduction can be attributed to activation of the receptors and not administration of the actuator drug itself.

Muscarinic M1 Receptors Modulate Working Memory Performance and Activity Via KCNQ Potassium Channels in Primate Prefrontal Cortex

2019 ◽  
Author(s):  
Veronica Claire Galvin ◽  
ShengTao Yang ◽  
Constantinos D. Paspalas ◽  
Yang Yang ◽  
Lu E. Jin ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Potassium Channels ◽  
Memory Performance ◽  
M1 Receptors

Prefrontal Hemodynamics of Physical Activity and Environmental Complexity During Cognitive Work

2017 ◽  
Vol 59 (1) ◽  
pp. 147-162 ◽  
Author(s):  
Ryan McKendrick ◽  
Ranjana Mehta ◽  
Hasan Ayaz ◽  
Melissa Scheldrup ◽  
Raja Parasuraman
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Selective Attention ◽  
Memory Performance ◽  
Physical Work ◽  
Environmental Complexity ◽  
Cognitive States ◽  
Executive Processing ◽  
Cognitive Work ◽  
Back Task

Objective: The aim of this study was to assess performance and cognitive states during cognitive work in the presence of physical work and in natural settings. Background: Authors of previous studies have examined the interaction between cognitive and physical work, finding performance decrements in working memory. Neuroimaging has revealed increases and decreases in prefrontal oxygenated hemoglobin during the interaction of cognitive and physical work. The effect of environment on cognitive-physical dual tasking has not been previously considered. Method: Thirteen participants were monitored with wireless functional near-infrared spectroscopy (fNIRS) as they performed an auditory 1-back task while sitting, walking indoors, and walking outdoors. Results: Relative to sitting and walking indoors, auditory working memory performance declined when participants were walking outdoors. Sitting during the auditory 1-back task increased oxygenated hemoglobin and decreased deoxygenated hemoglobin in bilateral prefrontal cortex. Walking reduced the total hemoglobin available to bilateral prefrontal cortex. An increase in environmental complexity reduced oxygenated hemoglobin and increased deoxygenated hemoglobin in bilateral prefrontal cortex. Conclusion: Wireless fNIRS is capable of monitoring cognitive states in naturalistic environments. Selective attention and physical work compete with executive processing. During executive processing loading of selective attention and physical work results in deactivation of bilateral prefrontal cortex and degraded working memory performance, indicating that physical work and concomitant selective attention may supersede executive processing in the distribution of mental resources. Application: This research informs decision-making procedures in work where working memory, physical activity, and attention interact. Where working memory is paramount, precautions should be taken to eliminate competition from physical work and selective attention.

scholarly journals Muscarinic M1 Receptors Modulate Working Memory Performance and Activity via KCNQ Potassium Channels in the Primate Prefrontal Cortex

Neuron ◽  
2020 ◽  
Vol 106 (4) ◽  
pp. 649-661.e4 ◽  
Author(s):  
Veronica C. Galvin ◽  
Sheng Tao Yang ◽  
Constantinos D. Paspalas ◽  
Yang Yang ◽  
Lu E. Jin ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Potassium Channels ◽  
Memory Performance ◽  
M1 Receptors

scholarly journals Goal-directed and stimulus-driven selection of internal representations

2020 ◽  
Vol 117 (39) ◽  
pp. 24590-24598
Author(s):  
Freek van Ede ◽  
Alexander G. Board ◽  
Anna C. Nobre
Keyword(s):  
Working Memory ◽  
Feature Matching ◽  
Memory Performance ◽  
Sensory Information ◽  
Internal Representations ◽  
Memory Representations ◽  
External Stimuli ◽  
Selection Of ◽  
Do So

Adaptive behavior relies on the selection of relevant sensory information from both the external environment and internal memory representations. In understanding external selection, a classic distinction is made between voluntary (goal-directed) and involuntary (stimulus-driven) guidance of attention. We have developed a task—the anti-retrocue task—to separate and examine voluntary and involuntary guidance of attention to internal representations in visual working memory. We show that both voluntary and involuntary factors influence memory performance but do so in distinct ways. Moreover, by tracking gaze biases linked to attentional focusing in memory, we provide direct evidence for an involuntary “retro-capture” effect whereby external stimuli involuntarily trigger the selection of feature-matching internal representations. We show that stimulus-driven and goal-directed influences compete for selection in memory, and that the balance of this competition—as reflected in oculomotor signatures of internal attention—predicts the quality of ensuing memory-guided behavior. Thus, goal-directed and stimulus-driven factors together determine the fate not only of perception, but also of internal representations in working memory.

Ecstasy use and higher-level cognitive functions: weak effects of ecstasy after control for potential confounds

2008 ◽  
Vol 38 (9) ◽  
pp. 1319-1330 ◽  
Author(s):  
G. Bedi ◽  
J. Redman
Keyword(s):  
Working Memory ◽  
Cognitive Functions ◽  
Verbal Memory ◽  
Drug Users ◽  
Memory Performance ◽  
Memory Function ◽  
Inverse Association ◽  
Cross Sectional ◽  
Cohort Design ◽  
Larger Sample

BackgroundAlthough there have been several reports linking ecstasy use with lowered cognitive function, much previous research suffers from substantial methodological limitations. The present study aimed to examine associations between ecstasy use and higher-level cognitive functions, using a larger sample size than most previous research and better controlling for a range of potential confounds.MethodA cross-sectional cohort design assessed 45 currently abstinent ecstasy polydrug users (EP), 48 cannabis polydrug users (CP) and 40 legal drug users (LD). Standardized neuropsychological tests were used to measure attention, verbal, visual and working memory and executive function. Prospective memory function was also assessed.ResultsIt was not possible to discriminate between groups on the basis of the cognitive functions assessed. Regression analyses showed an inverse association between lifetime dose of ecstasy and verbal memory performance. A combination of drug-use variables, including measures of ecstasy use, contributed to prediction of attention/working memory. However, individual associations were small, explaining 1–6% of variance in cognitive scores.ConclusionsAlthough the results suggest that heavy use of ecstasy is associated with some lowering of higher-level cognitive functions, they do not indicate a clinical picture of substantial cognitive dysfunction.

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